The present invention relates generally to methods, compounds and compositions for inhibiting effective binding of a chemokine to its cellular receptor. The compounds and compositions include cosalane and analogs thereof. The invention further relates to methods, compounds and compositions for treating inflammatory diseases.
Inflammation is a natural immune system response to injury or destruction of tissues and serves to destroy or otherwise confine an injurious agent or injured tissue. The inflammatory process includes targeting immune system and other cells to the site of damage to effect repairs. Although the response is generally protective in nature, in many cases it results in various disease states. A variety of molecules are involved in the inflammation process, including chemokines.
Chemokines are 8–15 Kda secreted chemoattractant proteins that are released by cells at a site of tissue injury and are regarded as important mediators of inflammation due to their ability to enhance migration of certain immune system cells, including, for example, T-cells, B-cells, basophils, neutrophils, and macrophages. Chemokines have been shown to induce directional leukocyte migration (chemotaxis) by binding to seven transmembrane G-coupled protein receptors (8). Chemokines also function to induce other inflammation-related events, including lysosomal enzyme release, respiratory burst, and histamine release. The chemokines and their receptors have been shown to participate in several disease states including allergy and asthma, (9,10) and angiogenesis during solid-tumor development (11). Inhibiting many of these undesired chemokine-induced processes may be beneficial in treating many inflammatory diseases. Compounds, compositions and methods of inhibiting chemokine-induced processes are thus needed. The present invention addresses this need.